Clinical effectiveness

Objectives

The overall aim of STRATEGIC was to determine whether or not uptake of cervical screening could be improved among 25-year-old women receiving their initial invitation. The trial was embedded in the NHS Cervical Screening Programme and conducted in two phases with the following objectives.

Phase 1 objectives

1. To determine, in an English cohort of 24.75-year-old women in Greater Manchester and a Scottish cohort of 20-year-old women in Grampian, the clinical effectiveness and cost-effectiveness of a pre-first invitation leaflet (pre-leaflet), which had been designed to increase receptivity of young women to cervical screening. The development of this leaflet had been completed prior to the trial, and was based on focus group work with young women, targeting the issues that influence them when thinking about attending for cervical screening.

2. To determine the feasibility, acceptability, clinical effectiveness and cost-effectiveness of offering online booking as a convenient alternative to telephoning the general practice as a means of making an appointment at first invitation. This was available only to the women covered by Manchester Primary Care Trust (PCT) (now redesignated a Clinical Commissioning Group).

3. To determine, among the 20-year-old women in Grampian, whether prior HPV vaccination in the catch-up campaign was associated with an increase or decrease in participation.

Phase 2 objectives

To determine, among those women in the cohort who had not attended after 6 months, the feasibility, acceptability, clinical effectiveness and cost-effectiveness of several novel strategies:

1. the offer of requesting a self-sampling kit (SSK) for HPV status as a determinant of the need for cervical cytology (HPV-negative women would not require cytology)

2. SSKs sent unsolicited to women

3. a specialist NN to help a woman overcome her barriers to screening 4. timed appointments for cervical screening to encourage women to attend 5. a choice of requesting a HPV SSK or the NN.

In addition, a health economic study (see Chapter 3) would be performed to determine the costs and cost-effectiveness of these interventions and a DCE (see Chapter 4) would be performed to determine the importance non-attending women attach to different aspects of the screening experience.

Methods

Phases 1 and 2 both comprised a cluster randomisation of general practices (Figure 1). All women invited for their first screen were eligible. Concurrent with phase 1, a pilot study tested the feasibility of the planned interventions to be evaluated during phase 2. A pre-leaflet had been developed prior to the STRATEGIC trial (see Appendices 1–3), based on focus group work with young women, and addressed issues that influenced their views.¹¹These included the relationship between cervical cancer and HPV, the sexually transmitted nature of HPV and why young women should be screened. The pre-leaflet was sent, by the screening agency in Greater Manchester and by the research team in Grampian, 6 weeks before

their standard invitation was sent out. Phase 1 also included the offer of online booking, which provided women in randomised practices restricted to Manchester PCT the option to choose from a selection of set appointments online, as an alternative to telephoning the general practitioner (GP). The phase 2 interventions, which were introduced after the pilot study, were sent out only to women without a cytology test recorded 6 months after their test due date. These included SSKs, either sent unsolicited or requested, timed appointments to have a cervical sample taken, access to a NN and a choice between the NN or a SSK. The primary outcomes were uptake of phase 1 interventions 3 months after the routine invitation and of phase 2 interventions 12 months after the invitation. The cervical screening process within the STRATEGIC trial can be seen in Figure 2. Data were obtained from the NHS screening agency, which also facilitated mailings.

Interaction with the screening agency

The STRATEGIC trial procedures were conducted differently in Greater Manchester and Grampian because of differing amounts of support from the screening agencies.

Phase 1: Parallel studies in Greater Manchester and Grampian Cluster randomise 180 general practices (83 Grampian) to send pre-cervical

screening leaflet 6 –12 weeks prior to first invitation (24.5 years/20 years)

Pre-leaflet No pre-leaflet

Phase 2: Greater Manchester and Grampian non-attenders (phase 1) before second reminder entered phase 2

Choice (NN or request HPV SSK) No further action

Request HPV SSK Timed appointments Unsolicited HPV SSK NN

Choice (NN or request HPV SSK) No further action

Randomised Randomised

Randomised

Randomised Randomised

FIGURE 1 The STRATEGIC study cluster randomisation: Greater Manchester and Grampian. a, Synchronous pilot studies on known non-attenders (age 25.5 years) to ensure the feasibility of HPV self-sampling, NNs and timed appointments; b, in Manchester PCT only.

Produce PNL for GP practice identifying women due to be screened

Run report to identify women aged 24 (20) years included for first call (use this report to create/update spreadsheet for monitoring

purpose)

Send pre-leaflet to women in cohort specified to receive pre-notification

Is woman included in cohort to receive details of online booking?

Send standard invitation letter to woman unless GP practice have advised woman

should be postponed/ceased

Is woman included in cohort to receive details of online booking?

Send standard reminder letter

Send non-responder notification to GP practice (card or via Open Exeter)

Run CSSE report to identify non responders to screening age 25 years – call/recall type

Split into six phase 2 intervention groups

Send standard invitation

FIGURE 2 Cervical screening process with STRATEGIC trial processes embedded (Scotland). This excludes pre-leaflet and includes online booking that was not done in Scotland. PNL, patient notification list.

Greater Manchester

Phase 1

The mailing of the phase 1 pre-leaflet took place weekly, and each week the screening agency recorded and returned a summary of these data to the trial team in Manchester. This summary included the number of pre-leaflets sent that week and the number of participants allocated to the control group that week.

This enabled the trial team to keep track of the study numbers for the duration of the trial. It also enabled the trial team to estimate the number of pre-leaflets and pre-paid envelopes the screening agency would require in future weeks and months.

In Manchester, for general practices allocated to the online booking arm, the screening agency inserted extra text into the standard invitation to screening and reminder letters. The extra text invited women to book a screening appointment at one of the community and sexual health (CaSH) clinics in Manchester.

Phase 2

Phase 2 interventions were sent by the screening agency to women who had no cytology test recorded 6 months after their test due date. The screening agency mailed out offers from the study team for the different interventions to eligible women. The screening agency provided a summary of interventions sent weekly to the trial team in Manchester. This was important, as they required the trial team in Manchester to order and maintain stock and supplies of SSKs and the stamps required to post them. Unusual activity prompted a query to the screening agency to ensure that the numbers were accurate.

Grampian

Phase 1

Because the screening agency in Grampian did not have the provision to assist the STRATEGIC trial team in the way the screening agency in Greater Manchester did, the team in Grampian were required to send the phase 1 interventions directly on a weekly basis. In Grampian, ATOS, the information technology company that developed and maintains the Scottish Cervical Call/Recall System (SCCRS), provided the trial team with a data extract of eligible women.

This extract was run weekly by the principal investigator in Grampian and the GP practices were then randomised to the phase 1 intervention. The pre-leaflets were posted by a member of the research team.

This was subsequently recorded weekly in a Microsoft Excel^®2003 (Microsoft Corporation, Redmond, WA, USA) format. The data were stored on a secure drive, in line with data protection policy. The vaccination status was extracted from the SCCRS, along with the screening outcome data transferred to the SCCRS by linkage with the Scottish Immunisation Record System. Data recorded include type of vaccine, number of doses and dates of doses administered.

Phase 2

A similar procedure was followed as in phase 1; however, the practicalities were more complicated. ATOS provided a data extract from the SCCRS of women eligible for phase 2. The data were downloaded using the extract by the Aberdeen principal investigator and were used during the preparation of data outcomes as a source document. In order to transform this data extract into a format that could be used by the trial team, a macro was developed to format the data extract into a tabulated layout. This included all women who were potentially eligible for phase 2, filtered to exclude those women with a cytology test result. This left a list of women who were eligible for a phase 2 intervention. A look-up query was added in order to establish which phase 2 intervention their GP practice had been randomised to, and the interventions were sent out.

All the steps above have been followed and records maintained, again stored on a secure drive, in line with University of Aberdeen data protection policies. This procedure was monitored by the trial co-ordinator based in Manchester and visits were made to the centre in Grampian in order for quality checks.

Interaction with general practices

Phase 1

Initial contact was made with the GPs by the trial team in order to introduce them to the trial. The research nurse attended the clinical commissioning group meetings prior to the STRATEGIC pilot study starting and provided a synopsis of the trial. Representatives from general practices were given the opportunity to make the trial team aware of any potential issues that they could foresee with the trial.

Next, a standard letter was sent to the general practice informing them of their trial arm allocation to a pre-leaflet or no pre-leaflet.

Phase 2

The next point of contact made to the general practice by the trial team was prior to the phase 2 interventions when the trial team informed them of the intervention to which their practice had been randomised. The timed appointments required the screening agency to send a standard letter to the general practice asking them to send eligible women an offer letter, detailing a time and date for them to attend for a cytology sample. The general practice then returned the letter to the agency with the date given to the woman. Once the trial team received a list of confirmed timed appointments, the general practice invoiced the trial team for reimbursement of £5 per letter.

Operationalising the interventions Phase 1

Pre-leaflet

The development of the pre-leaflet is described in Appendix 1. Once a general practice was randomised, the research team in Manchester produced a mail merge informing each general practice of the

intervention that they had been randomised to. Included in the letter was the contact details of the trial team, and the general practice were encouraged to contact the research team with any questions.

Once this initial contact had been made with the general practices, and phase 1 was ready to begin, the research team arranged a meeting with the screening agency in order to discuss the implementation of phase 1. The screening agency (as detailed previously), produced a weekly mailing for women eligible to take part in the STRATEGIC study; the intervention received by each woman depended on the intervention to which their general practice had been randomised. These figures were reported back to the trial team in Manchester on a weekly basis.

Online booking

Young women are more accustomed to using online services, so the provision of a web link that enabled women to book their screening test online could have been popular. It was not possible to offer this in general practice because of the large number of practices involved, but online booking was implemented for the CaSH clinics in the Manchester area. Online booking was not available in Salford/Trafford or in Grampian. A standalone online appointment scheduling system was used (www.supersaas.com/), and appointments were available throughout the day and at clinics across Manchester.

In order to offer this online booking service consistently and effectively, the trial team in Manchester implemented and a followed a strict standard operating procedure, and worked closely with the central CaSH clinic. The offer of booking an appointment for cervical screening online was sent by the screening agency. If a woman chose to respond, she would access the online system to select an appointment, with a choice of three clinics and selecting her preferred date and time, then leaving a contact name and telephone number. Each Friday, a member of the trial team would access the online system in order to remove the empty slots for the next week and inform the CaSH clinic of any booked appointments for the next week. Reminders were set for the day before each booked appointment as a reminder text message was sent by a member of the trial team, via the secure NHS.net system.

Pilot study

The pilot study was performed in Greater Manchester concurrently with phase 1 involving a slightly older cohort than the STRATEGIC cohort, and determined the feasibility of HPV self-sampling, both sent and requested, as well as the NNs and timed appointments being offered to known non-attendees in Manchester. The piloted interventions were tested in women who were already aged 25.5–27.5 years, who had previously not taken up their invitation for their first cervical screen, despite reminders.

Although the primary purpose of this pilot was to evaluate the feasibility of the intervention (e.g. arranging pre-booked appointments), as well as practicability such as arrangements for self-testing, it would also provide estimates of the likely effect on uptake of screening as a result.

Phase 2

Nurse navigator

Nurses offer support and guidance to patients, and offering a trained cervical screening nurse with whom women could discuss concerns or raise questions confidentially about screening may help alleviate their fears and‘navigate’ women over barriers to attending for screening. The NN would be able to discuss the woman’s perceived barrier(s) or difficulty accepting her invitation for cervical screening and advise how these could be overcome. She could also answer questions and assist the woman in booking an appointment if necessary.

Six months after their test due date, if no test date was recorded, women in general practices randomised to receive the NN intervention received a letter describing the trial along with a second reminder letter from the screening agency as per standard procedure. This letter (see Appendix 4) included the ways in which the women could contact the NN (via e-mail, telephone or text message), and the suggested ways in which the NN could offer advice or help. Once contact had been made with the NN, the role of the NN could be far-reaching, providing advice on the importance of cervical screening and how to attend a cervical screening appointment at their general practice, at a sexual health clinic or by sending them a HPV SSK. Written consent for any follow-up was sought by the NN at the time the woman made contact, and with her permission the consent forms and an information sheet were mailed out (see Appendix 5).

The consent enabled the trial team to check for the presence of a cytology test result on the national screening database, allowing our researchers to monitor compliance with screening after contact. Women were also offered a follow-up call from the NN to discuss whether or not they had arranged/attended for screening and to provide further advice or support.

Human papillomavirus self-sampling

Cervicovaginal self-testing for high-risk HPV triaged with cytology for the purpose of colposcopy referral is as sensitive in the detection of CIN as practitioner-obtained cytology at detecting CIN. This strategy accepts that a negative self-sample would allow a woman to be considered as having had a negative screen, whereas a positive result would indicate the need for practitioner-obtained cytology in order to achieve the required level of specificity for colposcopy referral. Women were offered a self-sample test for HPV to attract those who preferred not to attend their GP for a cytology sample.

There were two HPV self-sampling interventions; the first was a letter offering the opportunity to request a SSK, and the second an unrequested SSK was sent directly to the home. The SSK comprised the following:

a SSK [either Delphi lavage (Rovers Medical Devices BV, Oss, the Netherlands) or The Rovers^®Evalyn-Brush (Rovers Medical Devices BV, Oss, the Netherlands)]; and packaging, to return their sample, compliant with transport regulation UN3373 for category B biological substances.¹²

An information sheet explained the purposes of the test, how the results would be communicated to the woman and her GP, the implications of the results and instructions for taking the sample and returning it to the virology laboratory. A consent form for processing the sample and providing the results was included, giving her the option of receiving her result by a telephone call, text message, e-mail or letter.

The consent also obtained permission for the research team to check the Exeter screening database

(SCCRS in Grampian) for subsequent cytology samples in the event of a positive result. After the women collected the sample it was sent to the virology laboratory at Central Manchester University Hospitals NHS Foundation Trust for processing. The team at the laboratory sent the results and the consent forms to the trial team in Manchester University. The trial research nurse provided the HPV result as per the women’s preference (letter/telephone call/text/e-mail).

Choice between nurse navigator and human papillomavirus self-sampling

The rationale of using an intervention involving choice was to provide some women with a degree of control over what intervention they may prefer. Access to a nurse to provide advice and access to a SSK were felt to be sufficiently different to provide a meaningful choice. A letter was sent to women offering them either having access to a NN or a SSK on request.

Timed appointments

Timed appointments for non-responders have shown promise in other screening settings.^13,14Timed appointments mean that a woman does not have to contact the practice to book a cervical screening appointment herself. Agreement to set up timed appointments was achieved through contact with general practices. As with the implementation of the other STRATEGIC study interventions, the research team in Manchester sent a sample invitation letter to the screening agency it then sent this onto the general practices so that they could populate the letters with the time, date and women’s details, in order to offer them a timed appointment. In these letters, the general practices were asked to send women an invitation letter detailing a time and date for them to attend for a cervical screening appointment (see Appendix 6).

Only three general practices were unable to facilitate these appointments.

Patient and public involvement

We had planned to convene a panel of young women who had chosen not to attend for screening, in order to provide insight and advice regarding our interventions and the responses to these. We were not, however, able to use this proposed panel of users during the study. The principal reason for this was that we found it very difficult to engage with non-attenders for the DCE (see Chapter 4), which was required to be conducted at arm’s length in the sense that such women were contacted initially through the

We had planned to convene a panel of young women who had chosen not to attend for screening, in order to provide insight and advice regarding our interventions and the responses to these. We were not, however, able to use this proposed panel of users during the study. The principal reason for this was that we found it very difficult to engage with non-attenders for the DCE (see Chapter 4), which was required to be conducted at arm’s length in the sense that such women were contacted initially through the